Integrative Analysis of Circulating Tumor Cells Reveals Critical Gene Networks in Lung Cancer

Circulating tumor cells (CTCs) are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood. Understanding the metastatic cascade of CTCs has tremendous potential for identifying targets against cancer metastasis. Genomic instability contributes to tumor evolution and the emergence of resistant tumor subclones. Monitoring tumor genomic instability, especially in tumor resistance and metastasis, dramatically contributes to evaluating treatment response and precision medicine. The evaluation of CTCs assessment using noninvasive liquid biopsy is accessible for serial sampling to detect the genomic instability of the tumor. Clinically, CTCs are now used as surrogate biomarkers for many solid cancers. Numerous studies have been carried out, mainly in breast, prostate, lung, liver, pancreatic, gastric, and melanoma. In this study, we mainly present the role of CTCs as biomarkers for diagnosis, prognostication, and therapy monitoring in lung cancer patients using high-throughput data analyses and bioinformatics tools. Material and methods: Microarray data, including ۲۴ lung cancer patients at baseline tumor measurement and ۹ normal samples, were obtained from the GEO database (GSE ۲۴۹۲۶۲). The affy(۱.۸۲.۰) package in R (۴.۴.۱) was used to indicate gene expression profiling, evaluate data quality, and extract differentially expressed genes (DEG) between tumor and normal samples. |log۲FC| ≥۰.۵۸, and p-value< ۰.۰۵ cut-off were set to identify the significant differentially expressed genes. We performed a weighted gene co-expression network analysis to construct the co-expression network. We also conducted a preservation analysis to identify modules not preserved between tumor and normal tissues using the WGCNA package (۱.۷۲-۵). Then, two modules were selected to identify hub genes using the CytoHubba plugin in Cytoscape software (۳.۱۰.۲). Result: Our results indicated ۳۶۹ up-regulated genes and ۲۱۸ down-regulated genes in baseline tumors compared to normal samples. Co-expression network analysis revealed that the Orange and plum۱ modules were non-preserved in lung cancer samples. Two hub genes, including BDP۱, PLCL۲, significantly up-regulated in tumors vs normal samples. Conclusion: CTCs are released from primary tumors and transported through the body via blood or lymphatic vessels before settling to form micrometastases under suitable conditions. Accordingly, several studies have identified CTCs as a negative prognostic factor for survival in many types of cancer. Based on ۵۸۷ differential expressed genes and co-expression network analyses, these findings identify biomarkers that may contribute to cancer development. They provide a foundation for further exploration of CTC-derived biomarkers in lung cancer diagnosis, prognostication, and treatment monitoring. Future studies should focus on validating these biomarkers and investigating their functional roles in lung cancer pathology.

کلیدواژه ها:

Circulating tumor cells (CTCs) ، Lung cancer ، Differentially expressed genes (DEG) ، weighted gene co-expression network (WGCNA)